This proposal directly addresses the goal of PA-08-121 Symptom Interactions in Cancer and Immune Disorders issued by the National Institute of Nursing Research (NINR), National Cancer Institute (NCI), National Center on Complementary and Alternative Medicine (NCCAM), and National Institute on Aging (NIA), National Institutes of Health (NIH), soliciting research to design and test interventions targeted to interacting or clustered symptoms that are hypothesized to lead to beneficial patient outcomes. The overall goal of this biobehavioral, randomized clinical trial (RCT) is to examine the effects of an innovative, nonpharmacological symptom management modality, cranial microcurrent electrical stimulation (CES,) for ameliorating psychoneurologic symptoms (depression, anxiety, fatigue, pain and sleep disturbances) in women (N=150) with early-stage breast cancer (BC) over the adjuvant chemotherapy treatment period. CES is a non-invasive, portable, and easily standardized modality that been approved by the FDA as a drug-free treatment for depressed mood, anxiety, pain and insomnia. The proposed study builds on a NCI-funded pilot, feasibility study (R21 CA106149, Lyon, PI) of CES in women receiving chemotherapy for breast cancer. Results from our pilot study support the safety and feasibility of the use of CES during the adjuvant chemotherapy phase in women with early-stage breast cancer. Building on the findings of the pilot study, the primary aim of this RCT is to compare the effects of CES to sham CES over time on symptoms of depression, anxiety, fatigue, pain and sleep disturbances in women with early-stage breast cancer receiving adjuvant chemotherapy. Exploratory aims are to (1) explore the relationships among selected markers of inflammation (tumor necrosis factor alpha [TNF-1], interleukin-6 [IL-6], interleukin-IL1-2 [IL1-2], and C-reactive protein [CRP]), symptoms and QOL; (2) examine whether the symptoms of depression, anxiety, fatigue, sleep disturbances and pain form a cluster; and (3) examine the effects of CES on QOL. The specific aims will be accomplished using a prospective, randomized, sham-controlled, double-blinded clinical trial. A longitudinal repeated measures model will be used to compare the effects of the CES intervention to the sham control group over the adjuvant chemotherapy period. These findings could have valuable implications for symptom management of multiple common, distressing symptoms in oncology. Further, the proposed study will add to scientific understanding of the pattern of symptoms over time, the relationships of symptoms with markers of inflammation, and provide data for exploring the clustering of these symptoms.